来源：风湿病与关节炎,2019,8（6）:5-8,16.

机械应力失衡对大鼠软骨及软骨下骨的影响 （基础研究）

刘　静¹，孙智路¹，周　君^1,2，周桂娟¹，钟培瑞¹，成　果¹，王甜甜¹，邓程远¹，

廖　瑛¹

　　【摘　要】目的：观察关节内韧带切断后的关节不稳导致的机械应力改变引起的大鼠膝骨关节炎的关节软骨及软骨下骨的病理变化，为明确机械应力失衡在骨关节炎致病中的重要作用提供依据。方法：将30只3月龄Sprague-Dawley雄性大鼠随机分为对照组和模型组，每组15只。其中模型组手术切断前后交叉韧带、内侧副韧带，术后12周，眼眶取血，颈椎脱臼法处死实验大鼠，对各组大鼠行关节软骨的组织形态学观察及Mankin评分，对软骨下骨Micro-CT及骨组织显微结构进行定量分析。采用血清酶联免疫吸附法检测白细胞介素（IL）-1、IL-6、抗酒石酸酸性磷酸酶（TRACP-5b）、骨源性碱性磷酸酶（BALP）、Ⅱ型胶原C端肽（CTX-Ⅱ）水平。结果：①模型组关节软骨层变薄，软骨表面破损，部分软骨细胞核固缩，潮线紊乱，甲苯胺蓝染色减少。模型组Mankin评分较对照组明显增高，差异有统计学意义（P < 0.01）。②与对照组比较，模型组骨体积分数、骨小梁数量、骨小梁厚度显著降低，骨小梁分离度显著增高，差异有统计学意义（P < 0.05或P < 0.01）。③模型组血清IL-1、IL-6、TRACP-5b、BALP、CTX-Ⅱ水平较对照组均显著增高，差异有统计学意义（P < 0.01）。结论：采用前后交叉韧带、内侧副韧带切断，可以成功复制膝骨关节炎模型，模拟临床膝骨关节炎的病理变化，关节不稳所致的机械应力失衡是导致创伤性骨关节炎的重要因素。

　　【关键词】　骨关节炎，膝；机械应力；关节不稳；软骨；软骨下骨；大鼠

Effects of Mechanical Stress Imbalance on Cartilage and Subchondral Bone of Rats

LIU Jing,SUN Zhi-lu,ZHOU Jun,ZHOU Gui-juan,ZHONG Pei-rui,CHENG Guo,WANG Tian-tian,DENG Cheng-yuan,LIAO Ying

　　【ABSTRACT】Objective:To observe the pathological changes of articular cartilage and subchondral bone in rats with knee osteoarthritis caused by mechanical stress changes due to instability of intra-articular ligament after ligament transection,and to provide evidence for clarifying the important role of mechanical stress imbalance in the pathogenesis of osteoarthritis.Methods:Thirty three-month-old Sprague-Dawley male rats were randomly divided into a control group and a model group,with 15 rats in each group.In the model group,the anterior and posterior cruciate ligaments and medial collateral ligaments were cut off.Twelve weeks after operation,orbital blood was collected and cervical dislocation was used to kill the experimental rats.Histopathological observation and Mankin score were made for articular cartilage of each group.Micro-CT of subchondral bone and quantitative analysis of bone microstructure were also made.Levels of IL-1,IL-6,TRACP-5b,BALP and CTX-Ⅱ were measured by enzyme-linked immunosorbent assay.Results:①In model group,the articular cartilage layer became thinner,the surface of cartilage was damaged,some chondrocyte nuclei were pyknosis,tidal line was disordered,and toluidine blue staining was decreased.The Mankin score of the model group was significantly higher than that of the control group（P < 0.01）,the difference being statistically significant.②Compared with the control group,the bone volume fraction,trabecular number,and trabecular thickness obviously decreased and trabecular segregation decreased significantly in the model group,and the difference was statistically significant（P < 0.05 or P < 0.01）.③The levels of IL-1,IL-6,TRACP-5B,BALP and CTX-Ⅱ in the model group were significantly higher than those in the control group（P < 0.01）.Conclusion:By cutting the anterior and posterior cruciate ligaments and medial collateral ligaments,the model of knee osteoarthritis can be successfully reproduced and he pathological changes of clinical knee osteoarthritis can be simulated.The mechanical stress imbalance caused by joint instability is an important factor leading to traumatic osteoarthritis.

　　【Keywords】 osteoarthritis,knee;mechanical stress;joint instability;cartilage;subchondral bone;rats